The Science of Circadian Rhythms

Biologist Michael Rosbash’s groundbreaking research racks up accolades as his lab continues to decode what makes the fruit fly — and humans — tick.

Professor Michael Rosbash, director of the Brandeis National Center for Behavioral Genomics, has spent more than three decades studying circadian rhythms, the built-in biological clock that governs functions such as sleep and wakefulness, metabolism and hormone levels, in organisms as simple as fruit flies and as complex as humans.

Over the years, Rosbash’s lab, which includes post-docs, graduate students and undergraduates, has brought to light fundamental insights into the brain, health and disease, mental illness, and sleep disorders. These discoveries may lead to the eventual development of drugs to treat sleep disorders, physical and mental illness, and even jet lag.

International recognition and accolades have followed — almost like clockwork. The latest, the 2012 Wiley Prize in Biomedical Sciences, is the fifth major award he has won for discovering the molecular mechanisms of circadian rhythms in the fruit fly.

Rosbash, also an investigator with the Howard Hughes Medical Institute, will share the Wiley prize (a frequent precursor to the Nobel) with his longtime Brandeis collaborator and friend, Jeffrey Hall, now professor emeritus, and Michael Young of Rockefeller University. It will be presented to the trio April 5 at Rockefeller University in New York.

“We were incredibly fortunate to have advanced this problem in the remarkable way things have turned out,” says Rosbash. “Jeff and I, as well as Mike Young at Rockefeller, began these studies in the fruit fly with no certainty — in my case, no expectation — that the fly clockworks would be conserved in humans. So our work not only turned out to be interesting but also potentially important. How lucky can three guys get?”

At Brandeis, it’s not unusual for undergraduates to have the opportunity to work in a science lab. In Rosbash’s lab, Abigail Zadina ’13, a BS/MS candidate in neuroscience who’s worked in the lab for four years, started out as an assistant technician. Now she has funding to support research into tissue-specific gene expression and RNA editing.

The lab has its own rhythm. “The lab is very fast-paced and demanding,” says Zadina. “Professor Rosbash definitely asks a lot of people, but at the same time he’s very much interested in having his students do well, and is very keen on being there to make sure you’re getting the most out of every experience.”

In announcing the winners, Günter Blobel, chairman of the awards jury for the Wiley Prize, and a 1999 Nobel Prize winner said, “The molecular network discovered by these researchers imparts cyclic behavior to many biological processes, including sleep and wakefulness, metabolism and even the response to drugs.”

In 1984, Rosbash and Hall cloned the first circadian clock gene in the fruit fly Drosophila. Over the decades, the two behavioral geneticists made discovery after discovery about circadian genes using the fruit fly — a model organism valued for its relative genetic simplicity yet broad range of behaviors. Their remarkably fruitful partnership lasted until 2007, when Hall retired.

Operating in concert with the earth’s 24-hour rotation, circadian rhythms are the molecular machines that internally keep track of time in all plant and animal species. At the molecular level, circadian rhythms use the same genes and are regulated in much the same way in all animals, including humans.

Rosbash continues to refine his research, which is now focused on understanding in mechanistic detail how the fruit fly’s circadian timing occurs and how circadian gene expression is regulated. His lab is also studying which neural circuits are involved in circadian timekeeping and how individual circadian neurons function.